What is Rheumatoid Arthritis (RA)?
Chronic, systemic inflammatory disease of the joints and related structures
What is the pathophysiology related to RA?
- Immune-mediated inflammatory process
- Attacks synovium and other vital organs/tissues
- Erosive, symmetric joint involvement (frequently hands and feet)
- Chronic inflammation of synovial lining ( tissue exceeds borders and erodes into bone and cartilage within joint capsule pannus
- End result: joint destruction and deformity
What are key clinical features of RA?
- Morning stiffness that subsides after at least 30 minutes
- Stiff, painful, tender and/or swollen joints ("boggy" and warm to palpate)
- Progressively symmetrical presentation (Polyarticular)
Hand/Foot deformities (e.g. Swan-neck, Boutonniere, ulnar deviation, 'hammer' toe)
- Constitutional S/Sx
What is the primary objective and goal of therapy for RA?
Objective: To improve/maintain functional status and improve QOL
TX Goal: To relieve pain, preserve joint function and prevent/control joint destruction and systemic complications
What are non-drug therapy options for RA?
- Assistive devices
- Weight reduction/management
- Splinting/join protection
What are DMARDs?
(disease modifying anti-rheumatic drugs) a group of drugs that have potential to prevent joint damage
What is the MOST common monotherapy for RA?
Methotrexate (MTX); other may also be used
What are the most common Double DMARD therapy?
Any double combination of MTX, SSZ, HCQ, LEF
What is utilized in triple DMARD therapy?
MTX + SSZ + HCQ
What medications are classified as Non-biologic DMARDs? (4)
- Hydroxychloroquine (HCQ)
How does Hydroxychloroquine (HCQ) function?
Antimalarial; slows progression of erosive bone lesions (may induce remission); relatively fast onset (2-6 months; D/C if no response >6 months)
What are therapeutic uses for Hydroxychloroquine (HCQ)?
Combination (Double/Triple DMARD therapy)
- Reserved for RA unresponsive to NSAIDs
What should be monitored when utilizing Hydroxychloroquine (HCQ)?
- Ophthalmologic exam bi-annually (retinal toxicity)
- Does not cause liver/kidney/ bone toxicities
What are ADRs associated with Hydroxychloroquine (HCQ)?
GI: N/V/D (take with food)
Derm: pruritus, rash, alopecia, INC skin pigmentation
Neuro: HA, insomnia, vertigo
- Ocular Toxicity
How does Methotrexate (MTX) function?
Acts as immunosuppressive and anti-inflammatory agent (folic acid antagonist); slows appearance of new erosions
What are therapeutic uses for Methotrexate (MTX)?
- 1st LINE monotherapy DMARD
MAINSTAY moderate to severe RA (patients not responding to NSAIDs adequately)
What are ADRs for Methotrexate (MTX)?
GI: N/V/D, stomatitis (dose-related)
Hematologic: thrombocytopenia, leukopenia
Pulmonary: fibrosis, pneumonitis
Hepatic: ELEVATED liver enzymes, cirrhosis
What is a drug interaction with Methotrexate (MTX)?
NSAIDs (may DEC Clearance, INC ADRs)
What should be monitored when utilizing Methotrexate (MTX)?
Baseline: LFTs, CBC, Total bilirubin, HBV and HCV studies, serum Creatinine, albumin
Q1-2 months: CBC, AST, albumin
How does Sulfasalazine (SSZ) function?
PRODRUG cleaved in the colon to sulfapyridine (anti-rheumatic properties)
What are the therapeutic uses for Sulfasalazine (SSZ)?
What should be monitored when utilizing Sulfasalazine (SSZ)?
Month 1: CBC Q week
Continuing: CBC Q 1-2 months
How does Leflunomide (LEF) function?
Interferes with RNA/DNA synthesis in lymphocytes (reversible inhibitor of DHODH)
Reduces pain and inflammation associated with RA (slows progression of structural damage)
What are ADRs associated with Leflunomide (LEF)?
- Liver toxicity (CAUTION with Liver disease)
Pregnancy Category X (Wash cholestyramine out prior to conception)
What medications are classified as Tumor Necrosis Factor (TNF) Antagonist? (3)
How does Entanercept function?
Soluble TNF receptor that competitively binds 2 TNF molecules (renders inactive)
How do Infliximab and Adalimumab function?
Anti-TNF alpha monoclonal antibody (IgG) that inhibit progression of structural damage
What should be monitored when utilizing Anti-TNF agents?
- Initial tuberculin skin test
- Additive effects when in combination with Methotrexate (MTX)
Infliximab only: Human anti-chimeric molecule Ab development
- Infliximab only: Human anti-chimeric molecule Ab development
What ADRs are associated with Infliximab?
What ADRs are associated with Etanercept and Adalimumab?
Injection site reactions
What medications are classified as Interleukin-1 receptor Antagonist? (1)
Anakinra (TX moderate to severe RA)
How does Anakinra function?
- Slows degradation of cartilage and bone resorption
TX options: Monotherapy or Combo w/ MTX
What are ADRs associated with Anakinra?
- Similiar to Anti-TNF agents
- Injection site reactions
DO NOT USE combo with Anti-TNF (reserve for after Anti-TNF therapy is unsuccessful
What medications are classified as Non-TNF agents? (3)
How does Abatacept function?
Inhibits T-lymphocyte activation (soluble fusion protein)
TX options: monotherapy or combo
- VERY EXPENSIVE
How does Rituximab function?
Depletes B lymphocytes (reduces Ab formation)
Combo with MTX for moderate to severe cases with inadequate response to ANTI-TNF agents (FDA)
How does Tofacitinib function?
Inhibits Jaus kinase (JAK) enzymes (intracellular enzymes involved in stimulation of hematopoiesis and immune cell function)
BLACK BOX WARNING (infections and malignancy)
TX Option: monotherapy or combo W/ MTX or non-biologics (TX Moderate to severe RA)
Why are corticosteroids useful in RA treatment?
Could be used as a bridge to control debilitating symptoms until DMARDs take effect
What medications may alleviate ADRs associated with Methotrexate?